title: In vitro dissolution/permeation system to predict the oral absorption of poorly water-soluble drugs: effect of food and dose strength on it.
abstract: The aim of the present work was to confirm the usefulness of the dissolution/permeation system (D/P system) in the estimation of human oral absorption of poorly water-soluble drugs. The D/P system, which can simultaneously evaluate drug absorption processes, dissolution and permeation, can predict the oral absorption of poorly water-soluble drugs in fasted and fed humans, with a correlation between in vivo oral absorption (% of absorbed) and in vitro permeated amount (% of dose/2 h) in the D/P system. The oral absorption (fraction of absorbed dose, %) of poorly water-soluble drugs in the fasted and fed states was predicted using the D/P system. The effect of food on the oral absorption of various drugs estimated by the D/P system significantly correlated with clinical data (correlation coefficient: r(2)=0.924). Moreover, the proportion of oral absorption of cilostazol was predicted to decrease with an increase in its dose strength, which significantly correlated with in vivo human absorption. Consequently, the D/P system was demonstrated to be a useful in vitro system for prediction of the oral absorption of poorly water-soluble drugs.
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573–0101, Japan. makoto@pharm.setsunan.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Kataoka
authors.forename: Sachi
authors.initials: S
authors.lastname: Itsubata
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Masaoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000284:Administration, Oral; D018938:Caco-2 Cells; D000077407:Cilostazol; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000032:analysis*; D019518:Postprandial Period; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013777:Tetrazoles / Q000493:pharmacokinetics*; D014867:Water
chemical_list: D004364:Pharmaceutical Preparations; D013777:Tetrazoles; D014867:Water; D000077407:Cilostazol